Shock wave lithotripsy (SWL) is now used to manage almost 85 percent of all urinary stone patients. Yet, basic and clinical studies have demonstrated that SWL can induce acute and long-term bio-effects at both cellular and tissue levels. Moreover, SWL-induced tissue injury has been postulated to be linked either directly or indirectly with shock wave generated cavitation in vivo. Therefore, the overall goal of this proposed investigation is to assess quantitatively the inertial (? initial) cavitation and subsequent biological consequences generated by SWL in vivo. Two broad approaches will be undertaken: 1) to develop non-invasive techniques for the assessment of SWL-induced cavitation in vivo and its correlation with resultant tissue injury, and 2) to characterize and modulate the host responses in order to decrease inflammation and cell death. Our Specific Aims are as follows: Aim 1. To develop a new cavitation detection system with improved spatial resolution for the assessment of SWL-induced cavitation invivo. Cavitation threshold in different regions of the swine kidney will be determined using a hybrid cavitation detection/shock wave generator system of small focal size ( about 2mm). Aim 2. To examine wound healing in SWL-induced renal injury. Proinflammatory, cytokines, lipid peroxidation levels, and Cox-2 activity will be assessed in microdialysis samples, tissue sections, and blood samples in SWL-treated swine models. The effects of anti-oxidant and anti-inflammatory agents on SWL-induced renal damage will be determined. Aim 3. To assess dose-dependency of SWL-induced tissue injury. Characteristics in acoustic emission (AE) signals associated with SWL-induced bubble oscillations in tissue will be determined under clinically relevant lithotripsy conditions. A dose-dependent variation in the AE signals will be correlated with the corresponding changes in resultant tissue injury. Such a correlation could provide a non-invasive marker for assessing the progression of tissue injury in situ during SWL.